Determination of Levels of Micafungin in Neonates Suffering From Systemic Candidiasis and/or Candida Meningitis

NCT03421002 | Completed Phase 2

• 3 other identifiers: 9463-CL-60012014-003087-20800_OPBG_2014
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 2

Brief Summary

The primary purpose of this study is to evaluate the pharmacokinetic profile of micafungin administered to neonates suffering from systemic candidiasis. This study will also evaluate the proportion of success and of failure of the therapy with micafungin among treated neonates and will identify a conversion factor to relate plasma levels of micafungin into capillary and venous blood measured through blood samples from the heel and from a peripheral vein, collected simultaneously. Safety of micafungin in neonates will also be assessed.

Conditions

Candidiasis, Systemic; Candida Meningitis

Keywords

candida meningitis; Mycamine; candidiasis, systemic; micafungin

Outcome Measures

Primary Outcomes (2)

• Concentration of Micafungin in Blood

  Concentration will be determined from the pharmacokinetic (PK) blood samples collected via capillary micro-method (draws from the heel).

  Predose and after 1, 3, and 8 hours post-dose on one of treatment days from Day 3 to Day 10

• Concentration of Micafungin in Cerebral Spinal Fluid (CSF)

  Concentration will be determined from the from the CSF samples collected.

  Predose and after 1, 3, and 8 hours post-dose on one of treatment days from Day 3 to Day 10

Secondary Outcomes (4)

• Percentage of Participants with a Response at End of Treatment (EOT) - Success of Therapy (SOT)

  Up to day 14

• Percentage of Participants with A Response at EOT - Failure of Therapy (FOT)

  Up to day 14

• Number of Participants with Adverse Events (AEs)

  From the first dose of study drug administration up 72 hours after the last dose, up to 17 days

• Comparison of Capillary and Venous Plasma Concentrations of Micafungin

  Predose and after 1, 3, and 8 hours post-dose on one of treatment days from Day 3 to Day 10

Study Arms (1)

Micafungin

EXPERIMENTAL

Participants will receive micafungin 8 mg/kg per day via intravenous infusion for approximately 1 hour. Micafungin will be administered for a minimum of 14 days until 1 of the following conditions applied: •Negative results (absence of Candida growth) from at least 2 consecutive blood cultures and/or resolution of clinical and laboratory symptoms and reduction of mannan antigen blood level (\< 125 pg/mL) are obtained. •In case of meningitis, hydrocephalus and external ventricular derivation, negative results (absence of Candida growth) from at least 2 consecutive cerebral spinal fluid (CSF) cultures associated with resolution of clinical and laboratory symptoms. •Interruption (including addition or switch to another antifungal agent or dosage change of micafungin) due to demonstration of therapy failure.

Drug: Micafungin

Interventions

Micafungin DRUG

Participants will receive micafungin 8 mg/kg per day via intravenous infusion for approximately 1 hour.

Also known as: Mycamine

Micafungin

Eligibility Criteria

• Age: 1 Day - 180 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Infection by systemic candidiasis Systemic candidiasis is diagnosed in case of worsening of clinical conditions while on therapy with antibiotics, in case of isolation of candida from at least one sample collected from a normally sterile site (Blood, CSF, Urine, Peritoneal Fluid) and/or from at least two non contiguous sites (tracheal aspirate, gastric aspirate, faeces) and/or positivity to candida through polymerase chain reaction (PCR)(Septifast test), associated with at least one clinical symptom (fever or hypothermia, mottled skin, feeding difficulties, muscular hypotonia or hypertonia, apnoea crisis, bradycardia, tachycardia, hypotension, dyspnea, polypnea, desaturation) and one laboratory symptom (white blood cell \[WBC\] ≤5000/mm3 or WBC ≥20.000/mm3, immature to total neutrophil ratio \[I/T ratio\] \>2, Platelet count ≤100.000/mm3, C-reactive Protein \>0,5 mg/dL, Standard Base Excess \>-7 mmol/L, CSF pleocytosis-cells ≥ 6) and/or positivity to test Enzyme Linked Immuno-Sorbent Assay (ELISA) for the mannan antigen (≥125 pg/ml).
• Neonates affected by candida meningitis and/or hydrocephalus due to candida infection and/or bearing external ventricular derivation, until enrollment of at least 4 subjects with this characteristics.
• Parents of neonates, or legal representative, able to consent and comply with protocol requirements.
• Survival expectation not inferior to 3 days.

You may not qualify if:

• Acute hepatopathy (ammonium \> 200 µg/dL) or chronic hepatopathy.
• Known allergy or hypersensitivity to echinocandins or any of the excipients present in the formulation of the investigational product.

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead
• IRCCS, Ospedale Pediatrico Bambino Gesu: collaborator

Study Sites (2)

Site IT39001

Rome, 00146, Italy

Location

Site IT39002

Rome, 00186, Italy

Location

Related Publications (1)

• Auriti C, Goffredo BM, Ronchetti MP, Piersigilli F, Cairoli S, Bersani I, Dotta A, Bagolan P, Pai MP. High-Dose Micafungin in Neonates and Young Infants with Invasive Candidiasis: Results of a Phase 2 Study. Antimicrob Agents Chemother. 2021 Mar 18;65(4):e02494-20. doi: 10.1128/AAC.02494-20. Print 2021 Mar 18.

  PMID: 33558294 DERIVED

Related Links

• Link to Results on the Astellas Clinical Study Results website

MeSH Terms

Conditions

Candidiasis, Invasive

Interventions

Micafungin

Condition Hierarchy (Ancestors)

Candidiasis; Mycoses; Bacterial Infections and Mycoses; Infections; Invasive Fungal Infections

Intervention Hierarchy (Ancestors)

Lipopeptides; Lipids; Peptides; Amino Acids, Peptides, and Proteins; Echinocandins; Peptides, Cyclic

Study Officials

• Executive Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2018
• First Posted: February 5, 2018
• Study Start: May 30, 2015
• Primary Completion: April 10, 2018
• Study Completion: April 10, 2018
• Last Updated: November 18, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2)